Abstract |
Polybrominated diphenyl ethers ( PBDEs) are an important class of halogenated organic brominated flame retardants. Because of their presence in abiotic and biotic environments widely and their structural similarity to polychlorinated biphenyls ( PCBs), concern has been raised on their possible adverse health effects to humans. This study was designed to determine the anti-proliferative, apoptotic properties of decabrominated diphenyl ether (PBDE-209), using a human hepatoma Hep G2 line as a model system. Hep G2 cells were cultured in the presence of PBDE-209 at various concentrations (1.0-100.0 micromol/L) for 72 h and the percentage of cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results showed that PBDE-209 inhibited the cells viability in time and concentration-dependent characteristics at concentrations (10.0-100.0 micromol/L). We found that anti-proliferative effect of PBDE-209 was associated with apoptosis on Hep G2 cells by determinations of morphological changes, cell cycle and apoptosis. Mechanism study showed that PBDE-209 could increase the generation of intracellular reactive oxygen species (ROS) concentration-dependently. Antioxidant N-acetylcyteine partially inhibited the increase of ROS. The mechanism for its hepatoma-inhibitory effects was the induction of cellular apoptosis through ROS generation. In addition, activity of lactate dehydrogenase (LDH) release increased when the cells incubated with PBDE-209 at various concentrations and times. These results suggested that PBDE-209 had the toxicity activity of anti-proliferation and induction of apoptosis in tumor cells in vitro.
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Authors | Xiao-Zhong Hu, Ying Xu, De-Cong Hu, Yang Hui, Fang-Xing Yang |
Journal | Toxicology letters
(Toxicol Lett)
Vol. 171
Issue 1-2
Pg. 19-28
(Jun 15 2007)
ISSN: 0378-4274 [Print] Netherlands |
PMID | 17509781
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2',7'-dichlorodihydrofluorescein diacetate
- Fluoresceins
- Free Radical Scavengers
- Halogenated Diphenyl Ethers
- Phenyl Ethers
- Polybrominated Biphenyls
- Reactive Oxygen Species
- decabromobiphenyl ether
- Acetylcysteine
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Topics |
- Acetylcysteine
(pharmacology)
- Apoptosis
(drug effects)
- Carcinoma, Hepatocellular
(metabolism, pathology, physiopathology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Dose-Response Relationship, Drug
- Flow Cytometry
- Fluoresceins
(pharmacology)
- Free Radical Scavengers
(pharmacology)
- G1 Phase
(drug effects)
- Halogenated Diphenyl Ethers
- Humans
- Liver Neoplasms
(metabolism, pathology, physiopathology)
- Phenyl Ethers
(pharmacology)
- Polybrominated Biphenyls
(pharmacology)
- Reactive Oxygen Species
(metabolism)
- Resting Phase, Cell Cycle
(drug effects)
- S Phase
(drug effects)
- Time Factors
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